Sotorasib Plus Panitumumab Dubbed New Standard Care for Metastatic Colorectal Cancer

The combination of sotorasib and panitumumab outperformed investigator’s choice of therapy in a phase 3 trial of patients with chemorefractory, KRAS^G12C-mutated metastatic colorectal cancer (CRC).

Researchers tested the combination with 2 different doses of sotorasib and found improved progression-free survival (PFS) at both doses. However, outcomes were better with the higher dose of sotorasib.

“Sotorasib 960 mg plus panitumumab is a potential new standard-of-care therapy for patients with previously treated, KRAS^G12C-mutated metastatic colorectal cancer,” said study investigator Filippo Pietrantonio, MD, of Fondazione IRCCS – Istituto Nazionale dei Tumori in Milan, Italy.

Dr Pietrantonio presented these findings, from the phase 3 CodeBreak 300 study (ClinicalTrials.gov Identifier: NCT05198934), at the ESMO Congress 2023.

CodeBreak 300 enrolled 160 patients with KRAS^G12C-mutated metastatic CRC who had received at least 1 prior line of therapy and had disease progression on or after fluoropyrimidine, irinotecan, and oxaliplatin.

Patients were randomly assigned to 1 of 3 treatment arms:

• Sotorasib at 960 mg daily plus panitumumab at 6 mg/kg every 2 weeks (n=53)
• Sotorasib at 240 mg daily plus panitumumab at 6 mg/kg every 2 weeks (n=53)
• Investigator’s choice of trifluridine/tipiracil or regorafenib (n=54).

Baseline characteristics were generally well balanced between the arms. The objective response rate was 26% in the 960 mg sotorasib-panitumumab arm, 6% in the 240 mg sotorasib-panitumumab arm, and 0% in the investigator’s choice arm. Disease control rates were 72%, 68%, and 46%, respectively.

At a median follow-up of 7.8 months, the median PFS was:

• 2.2 months in the investigator’s choice arm
• 3.9 months in the 240 mg sotorasib-panitumumab arm (hazard ratio [HR], 0.58; 95% CI, 0.36-0.93; P =.030)
• 5.6 months in the 960 mg sotorasib-panitumumab arm (HR, 0.49; 95% CI, 0.30-0.80; P =.006).

Overall survival data were not mature at the data cutoff.

The rate of grade 3 or higher treatment-related adverse events (TRAEs) was 36% in the 960 mg arm, 30% in the 240 mg arm, and 43% in the investigator’s choice arm. There were no fatal TRAEs in any arm.

The most common grade 3 or higher TRAEs with sotorasib and panitumumab were dermatitis acneiform, hypomagnesemia, rash, and diarrhea. The most common grade 3 or higher TRAEs in the investigator’s choice arm were neutropenia, nausea, and anemia.

Disclosures: This research was supported by Amgen Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for a full list of disclosures.

References

1. Pietrantonio F, Salvatore L, Esaki T, et al. Sotorasib plus panitumumab versus standard-of-care for chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC): CodeBreak 300 phase III study. Presented at ESMO Congress 2023. Oct 20-24, 2023. Madrid, Spain. Abstract LBA10.

Fakih MG, Salvatore L, Esaki T, et al. Sotorasib plus panitumumab in refractory colorectal cancer with mutated KRAS G12C. N Engl J Med. Published online October 22, 2023. doi:10.1056/NEJMoa2308795

This article originally appeared on Cancer Therapy Advisor